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Diabetologia
Published in: Diabetologia 2/2020

Open Access 01-02-2020 | Type 1 Diabetes | Article

Autoimmunity plays a role in the onset of diabetes after 40 years of age

Authors: Olov Rolandsson, Christiane S. Hampe, Stephen J. Sharp, Eva Ardanaz, Heiner Boeing, Guy Fagherazzi, Francesca Romana Mancini, Peter M. Nilsson, Kim Overvad, Maria-Dolores Chirlaque, Miren Dorronsoro, Marc J. Gunter, Rudolf Kaaks, Timothy J. Key, Kay-Tee Khaw, Vittorio Krogh, Tilman Kühn, Domenico Palli, Salvatore Panico, Carlotta Sacerdote, Maria-José Sánchez, Gianluca Severi, Annemieke M. W. Spijkerman, Rosario Tumino, Yvonne T. van der Schouw, Elio Riboli, Nita G. Forouhi, Claudia Langenberg, Nicholas J. Wareham

Published in: Diabetologia | Issue 2/2020

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Abstract

Aims/hypothesis

Type 1 and type 2 diabetes differ with respect to pathophysiological factors such as beta cell function, insulin resistance and phenotypic appearance, but there may be overlap between the two forms of diabetes. However, there are relatively few prospective studies that have characterised the relationship between autoimmunity and incident diabetes. We investigated associations of antibodies against the 65 kDa isoform of GAD (GAD65) with type 1 diabetes and type 2 diabetes genetic risk scores and incident diabetes in adults in European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct, a case-cohort study nested in the EPIC cohort.

Methods

GAD65 antibodies were analysed in EPIC participants (over 40 years of age and free of known diabetes at baseline) by radioligand binding assay in a random subcohort (n = 15,802) and in incident diabetes cases (n = 11,981). Type 1 diabetes and type 2 diabetes genetic risk scores were calculated. Associations between GAD65 antibodies and incident diabetes were estimated using Prentice-weighted Cox regression.

Results

GAD65 antibody positivity at baseline was associated with development of diabetes during a median follow-up time of 10.9 years (HR for GAD65 antibody positive vs negative 1.78; 95% CI 1.43, 2.20) after adjustment for sex, centre, physical activity, smoking status and education. The genetic risk score for type 1 diabetes but not type 2 diabetes was associated with GAD65 antibody positivity in both the subcohort (OR per SD genetic risk 1.24; 95% CI 1.03, 1.50) and incident cases (OR 1.97; 95% CI 1.72, 2.26) after adjusting for age and sex. The risk of incident diabetes in those in the top tertile of the type 1 diabetes genetic risk score who were also GAD65 antibody positive was 3.23 (95% CI 2.10, 4.97) compared with all other individuals, suggesting that 1.8% of incident diabetes in adults was attributable to this combination of risk factors.

Conclusions/interpretation

Our study indicates that incident diabetes in adults has an element of autoimmune aetiology. Thus, there might be a reason to re-evaluate the present subclassification of diabetes in adulthood.
Appendix
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Metadata
Title
Autoimmunity plays a role in the onset of diabetes after 40 years of age
Authors
Olov Rolandsson
Christiane S. Hampe
Stephen J. Sharp
Eva Ardanaz
Heiner Boeing
Guy Fagherazzi
Francesca Romana Mancini
Peter M. Nilsson
Kim Overvad
Maria-Dolores Chirlaque
Miren Dorronsoro
Marc J. Gunter
Rudolf Kaaks
Timothy J. Key
Kay-Tee Khaw
Vittorio Krogh
Tilman Kühn
Domenico Palli
Salvatore Panico
Carlotta Sacerdote
Maria-José Sánchez
Gianluca Severi
Annemieke M. W. Spijkerman
Rosario Tumino
Yvonne T. van der Schouw
Elio Riboli
Nita G. Forouhi
Claudia Langenberg
Nicholas J. Wareham
Publication date
01-02-2020
Publisher
Springer Berlin Heidelberg
Published in
Diabetologia / Issue 2/2020
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-019-05016-3

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